A practical approach to the treatment of depression in patients with chronic kidney disease and end-stage renal disease
2011; Elsevier BV; Volume: 81; Issue: 3 Linguagem: Inglês
10.1038/ki.2011.358
ISSN1523-1755
AutoresS. Susan Hedayati, Venkata Yalamanchili, Fredric O. Finkelstein,
Tópico(s)Electroconvulsive Therapy Studies
ResumoDepression is a common, under-recognized, and under-treated problem that is independently associated with increased morbidity and mortality in CKD patients. However, only a minority of CKD patients with depression are treated with antidepressant medications or nonpharmacologic therapy. Reasons for low treatment rates include a lack of properly controlled trials that support or refute efficacy and safety of various treatment regimens in CKD patients. The aim of this manuscript is to provide a comprehensive review of studies exploring depression treatment options in CKD. Observational studies as well as small trials suggest that certain serotonin-selective reuptake inhibitors may be safe to use in patients with advanced CKD and ESRD. These studies were limited by small sample sizes, lack of placebo control, and lack of formal assessment for depression diagnosis. Nonpharmacologic treatments were explored in selected ESRD samples. The most promising data were reported for frequent hemodialysis and cognitive behavioral therapy. Alternative proposed therapies include exercise training regimens, treatment of anxiety, and music therapy. Given the association of depression with cardiovascular events and mortality, and the excessive rates of cardiovascular death in CKD, it becomes imperative to not only investigate whether treatment of depression is efficacious, but also whether it would result in a reduction in morbidity and mortality in this patient population. Depression is a common, under-recognized, and under-treated problem that is independently associated with increased morbidity and mortality in CKD patients. However, only a minority of CKD patients with depression are treated with antidepressant medications or nonpharmacologic therapy. Reasons for low treatment rates include a lack of properly controlled trials that support or refute efficacy and safety of various treatment regimens in CKD patients. The aim of this manuscript is to provide a comprehensive review of studies exploring depression treatment options in CKD. Observational studies as well as small trials suggest that certain serotonin-selective reuptake inhibitors may be safe to use in patients with advanced CKD and ESRD. These studies were limited by small sample sizes, lack of placebo control, and lack of formal assessment for depression diagnosis. Nonpharmacologic treatments were explored in selected ESRD samples. The most promising data were reported for frequent hemodialysis and cognitive behavioral therapy. Alternative proposed therapies include exercise training regimens, treatment of anxiety, and music therapy. Given the association of depression with cardiovascular events and mortality, and the excessive rates of cardiovascular death in CKD, it becomes imperative to not only investigate whether treatment of depression is efficacious, but also whether it would result in a reduction in morbidity and mortality in this patient population. Major depressive disorder, defined as a clinical syndrome lasting for 2 weeks during which time the patient experiences either depressed mood or anhedonia plus at least 5 of the 9 Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) criterion symptom domains,1.Snow V. Lascher S. Mottur-Pilson C. Pharmacologic treatment of acute major depression and dysthymia.Ann Intern Med. 2000; 132: 738-742Crossref PubMed Scopus (124) Google Scholar,2.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edn,. American Psychiatric Association, Washington, DC1994Google Scholar is very common among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) and is associated with adverse outcomes.3.Hedayati S.S. Bosworth H.B. Kuchibhatla M. et al.The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients.Kidney Int. 2006; 69: 1662-1668Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar, 4.Hedayati S.S. Bosworth H. Briley L. et al.Death or hospitalization of patients on chronic hemodialysis is associated with a physician-based diagnosis of depression.Kidney Int. 2008; 74: 930-936Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar, 5.Hedayati S.S. Grambow S.C. Szczech L.A. et al.Physician-diagnosed depression as a correlate of hospitalizations in patients receiving long-term hemodialysis.Am J Kidney Dis. 2005; 46: 642-649Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar, 6.Kimmel P.L. Peterson R.A. Weihs K.L. et al.Multiple measurements of depression predict mortality in a longitudinal study of chronic hemodialysis outpatients.Kidney Int. 2000; 57: 2093-2098Abstract Full Text Full Text PDF PubMed Scopus (445) Google Scholar, 7.Lopes A.A. Bragg J. Young E. et al.Depression as a predictor of mortality and hospitalization among hemodialysis patients in the United States and Europe.Kidney Int. 2002; 62: 199-207Abstract Full Text Full Text PDF PubMed Scopus (431) Google Scholar, 8.Boulware L.E. Liu Y. Fink N.E. et al.Temporal relation among depression symptoms, cardiovascular disease events, and mortality in end-stage renal disease: contribution of reverse causality.Clin J Am Soc Nephrol. 2006; 1: 496-504Crossref PubMed Scopus (143) Google Scholar, 9.Hedayati S.S. Minhajuddin A.T. Afshar M. et al.Association between major depressive episodes in patients with chronic kidney disease and initiation of dialysis, hospitalization, or death.JAMA. 2010; 303: 1946-1953Crossref PubMed Scopus (164) Google Scholar Whereas depression point prevalence is 2–10% in the general population,10.Kessler R.C. Berglund P. Demler O. et al.The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication.JAMA. 2003; 289: 3095-3105Crossref PubMed Scopus (6308) Google Scholar 20% of CKD patients suffer from a major depressive episode,11.Hedayati S.S. Minhajuddin A.T. Toto R.D. et al.Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar,12.Watnick S. Kirwin P. Mahnensmith R. et al.The prevalence and treatment of depression among patients starting dialysis.Am J Kidney Dis. 2003; 41: 105-110Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar a prevalence even higher than reported for other chronic diseases such as diabetes mellitus and congestive heart failure.13.Anderson R.J. Freedland K.E. Clouse R.E. et al.The prevalence of comorbid depression in adults with diabetes.Diabetes Care. 2001; 24: 1069-1078Crossref PubMed Scopus (2972) Google Scholar,14.Jiang W. Alexander J. Christopher E. et al.Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure.Arch Intern Med. 2001; 161: 1849-1856Crossref PubMed Scopus (761) Google Scholar Depression results in substantial functional impairment and decreased quality of life in ESRD patients,15.Walters B.A. Hays R.D. Spritzer K.L. et al.Health-related quality of life, depressive symptoms, anemia, and malnutrition at hemodialysis initiation.Am J Kidney Dis. 2001; 40: 1185-1194Abstract Full Text Full Text PDF Scopus (167) Google Scholar, 16.Drayer R.A. Piraino B. Reynolds 3rd., C.F. et al.Characteristics of depression in hemodialysis patients: symptoms, quality of life and mortality risk.Gen Hosp Psychiatry. 2006; 28: 306-312Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar, 17.Peng Y.S. Chiang C.K. Hung K.Y. et al.The association of higher depressive symptoms and sexual dysfunction in male haemodialysis patients.Nephrol Dial Transplant. 2007; 22: 857-861Crossref PubMed Scopus (57) Google Scholar and levels of depression and functional and occupational impairment do not remit spontaneously in untreated depressed patients.18.Soykan A. Boztas H. Kutlay S. et al.Depression and its 6-month course in untreated hemodialysis patients: a preliminary prospective follow-up study in Turkey.Int J Behav Med. 2004; 11: 243-246Crossref PubMed Scopus (18) Google Scholar We showed that ESRD patients on chronic hemodialysis (HD) with depression are twice as likely to die or require hospitalization within a year as compared with those without depression,4.Hedayati S.S. Bosworth H. Briley L. et al.Death or hospitalization of patients on chronic hemodialysis is associated with a physician-based diagnosis of depression.Kidney Int. 2008; 74: 930-936Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar and are at risk for a 30% increase in both cumulative hospital days and number of hospitalizations.5.Hedayati S.S. Grambow S.C. Szczech L.A. et al.Physician-diagnosed depression as a correlate of hospitalizations in patients receiving long-term hemodialysis.Am J Kidney Dis. 2005; 46: 642-649Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar In a recent prospective observational cohort study of consecutively recruited stage 2–5 CKD predialysis patients, a diagnosis of current major depressive episode at baseline was associated with an increased risk of a composite of death, hospitalization, or progression to dialysis, independent of comorbidities and kidney disease severity (adjusted hazard ratio 1.86, 95% confidence interval 1.23, 2.84).9.Hedayati S.S. Minhajuddin A.T. Afshar M. et al.Association between major depressive episodes in patients with chronic kidney disease and initiation of dialysis, hospitalization, or death.JAMA. 2010; 303: 1946-1953Crossref PubMed Scopus (164) Google Scholar Despite the high prevalence of depressive symptoms as well as depressive disorder among patients with CKD and ESRD and its association with poor outcomes, only a minority of chronic dialysis patients receive adequate diagnosis and treatment for depression.3.Hedayati S.S. Bosworth H.B. Kuchibhatla M. et al.The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients.Kidney Int. 2006; 69: 1662-1668Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar, 12.Watnick S. Kirwin P. Mahnensmith R. et al.The prevalence and treatment of depression among patients starting dialysis.Am J Kidney Dis. 2003; 41: 105-110Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar, 19.Lopes A.A. Albert J.M. Young E.W. et al.Screening for depression in hemodialysis patients: associations with diagnosis, treatment, and outcomes in the DOPPS.Kidney Int. 2004; 66: 2047-2053Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar For example, in a retrospective analysis of the African American Study of Kidney Disease and Hypertension Cohort Study, Fischer et al.20.Fischer M.J. Kimmel P.L. Greene T. et al.Socioeconomic factors contribute to the depressive affect among African Americans with chronic kidney disease.Kidney Int. 2010; 77: 1010-1019Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar reported that only 20% of CKD participants with a Beck Depression Inventory (BDI) score of >14 (above the threshold validated for depression) were prescribed antidepressant medications. Similarly, Watnick et al.12.Watnick S. Kirwin P. Mahnensmith R. et al.The prevalence and treatment of depression among patients starting dialysis.Am J Kidney Dis. 2003; 41: 105-110Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar reported that only 16% of ESRD patients initiating chronic HD with BDI scores of ≥15 were on antidepressants. In a prospective observational cohort of 98 prevalent HD patients, nephrologists were informed about a current diagnosis of depressive disorder based on DSM IV diagnostic criteria in 26% of cases.4.Hedayati S.S. Bosworth H. Briley L. et al.Death or hospitalization of patients on chronic hemodialysis is associated with a physician-based diagnosis of depression.Kidney Int. 2008; 74: 930-936Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar However, intervention was made in only 23% of these patients, defined as referral to mental health clinic, initiation of an antidepressant medication, or increasing the dose of previously prescribed antidepressant. Thus, a major challenge for clinicians is to develop strategies to better understand and manage depression in CKD patients. However, there are limited data on safety and efficacy of antidepressant medications in patients with advanced CKD and ESRD. In addition, instituting effective treatment programs for depression in this patient population is challenging.20.Fischer M.J. Kimmel P.L. Greene T. et al.Socioeconomic factors contribute to the depressive affect among African Americans with chronic kidney disease.Kidney Int. 2010; 77: 1010-1019Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Recently, attention has begun to be focused on a variety of treatment strategies that may show future promise in selected groups of patients. The purpose of the present manuscript is to review the available evidence on treatment of depression in CKD patients. Given the high prevalence of depression in CKD patients and the association of depression with poor outcomes and reduced health-related quality of life, it is suggested that depression screening be integrated into routine patient care. Screening can take place on initial presentation of CKD patients for evaluation in clinic, at dialysis initiation for ESRD patients, and perhaps 6 months after initiation, and yearly thereafter.3.Hedayati S.S. Bosworth H.B. Kuchibhatla M. et al.The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients.Kidney Int. 2006; 69: 1662-1668Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar Several studies validated commonly used depression screening self-report questionnaires against DSM IV-based structured interviews among patients with CKD and ESRD3.Hedayati S.S. Bosworth H.B. Kuchibhatla M. et al.The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients.Kidney Int. 2006; 69: 1662-1668Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar, 11.Hedayati S.S. Minhajuddin A.T. Toto R.D. et al.Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 21.Watnick S. Wang P.L. Demadura T. et al.Validation of 2 depression screening tools in dialysis patients.Am J Kidney Dis. 2005; 46: 919-924Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar, 22.Craven J.L. Rodin G.M. Littlefield C. The Beck Depression Inventory as a screening device for major depression in renal dialysis patients.Int J Psychiatry Med. 1988; 18: 365-374Crossref PubMed Google Scholar. Table 1 lists the screening characteristics of these questionnaires, which can generally be completed in a few minutes. Any of these validated scales can be used to screen patients in CKD clinic or dialysis facilities. As seen here, the cutoff scores with the best diagnostic accuracy for depressive disorder in patients with predialysis stage 2–5 CKD were similar to cutoffs used in the general population (Table 1).Table 1Screening characteristics of self-report depression scales in CKD and ESRDScaleNo. of itemsScore, rangeCutoff score in general populationCutoff score in CKD (sensitivity, specificity)Cutoff score in ESRD (sensitivity, specificity)BDI3.Hedayati S.S. Bosworth H.B. Kuchibhatla M. et al.The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients.Kidney Int. 2006; 69: 1662-1668Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar, 11.Hedayati S.S. Minhajuddin A.T. Toto R.D. et al.Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 21.Watnick S. Wang P.L. Demadura T. et al.Validation of 2 depression screening tools in dialysis patients.Am J Kidney Dis. 2005; 46: 919-924Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar, 22.Craven J.L. Rodin G.M. Littlefield C. The Beck Depression Inventory as a screening device for major depression in renal dialysis patients.Int J Psychiatry Med. 1988; 18: 365-374Crossref PubMed Google Scholar210–63≥10≥11 (89%, 88%)≥14–16 (62–91%, 81–86%)QIDS-SR11.Hedayati S.S. Minhajuddin A.T. Toto R.D. et al.Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar160–27≥10≥10 (91%, 88%)CESD3.Hedayati S.S. Bosworth H.B. Kuchibhatla M. et al.The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients.Kidney Int. 2006; 69: 1662-1668Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar200–60≥16≥18 (69%, 83%)PHQ21.Watnick S. Wang P.L. Demadura T. et al.Validation of 2 depression screening tools in dialysis patients.Am J Kidney Dis. 2005; 46: 919-924Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar90–27≥10≥10 (92%, 92%)Abbreviations: BDI, Beck Depression Inventory; CESD, Center for Epidemiologic Studies Depression Scale; CKD, chronic kidney disease; ESRD, end-stage renal disease; PHQ, Patient Health Questionnaire; QIDS-SR, 16-Item Quick Inventory of Depressive Symptomatology Self-Report. Open table in a new tab Abbreviations: BDI, Beck Depression Inventory; CESD, Center for Epidemiologic Studies Depression Scale; CKD, chronic kidney disease; ESRD, end-stage renal disease; PHQ, Patient Health Questionnaire; QIDS-SR, 16-Item Quick Inventory of Depressive Symptomatology Self-Report. However, the cutoffs for those with ESRD were generally higher, perhaps because of more frequent presence of somatic symptoms in ESRD that may not be manifest in earlier CKD stages.11.Hedayati S.S. Minhajuddin A.T. Toto R.D. et al.Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar Thus, somatic symptoms, such as fatigue, loss of energy, decreased appetite, sleep disturbance, and difficulty concentrating, suggestive of depressive affect, may be more commonly reported by ESRD patients.19.Lopes A.A. Albert J.M. Young E.W. et al.Screening for depression in hemodialysis patients: associations with diagnosis, treatment, and outcomes in the DOPPS.Kidney Int. 2004; 66: 2047-2053Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar, 23.Abdel-Kader K. Unruh M.L. Weisbord S.D. Symptom burden, depression, and quality of life in chronic and end-stage kidney disease.Clin J Am Soc Nephrol. 2009; 4: 1057-1064Crossref PubMed Scopus (319) Google Scholar, 24.Cukor D. Cohen S.D. Peterson R.A. et al.Psychosocial aspects of chronic disease: ESRD as a paradigmatic illness.J Am Soc Nephrol. 2007; 18: 3042-3055Crossref PubMed Scopus (281) Google Scholar, 25.Kurella M. Luan J. Lash J.P. et al.Self-assessed sleep quality in chronic kidney disease.Int Urol Nephrol. 2005; 37: 159-165Crossref PubMed Scopus (39) Google Scholar However, for a definitive diagnosis of depressive disorder based on DSM IV, either feelings of sadness (depressed mood) or loss of interest (anhedonia) must accompany these symptoms.2.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edn,. American Psychiatric Association, Washington, DC1994Google Scholar If sadness or anhedonia is absent, consideration should be given to other causes such as dialysis inadequacy, poor nutritional status, cognitive dysfunction, dementia, and/or exacerbation of other comorbid illnesses, such as congestive heart failure (Figure 1). To help distinguish these symptoms, a structured interview should be performed to confirm a depressive disorder in patients who screen positive before treatment is considered. This can be performed by any of several individuals working in the clinic or dialysis facility (nephrologists or trained social workers and/or nurses). Alternatively, referrals can be made to mental health professionals, if clinically indicated; but this approach may present logistical problems in terms of reimbursement issues and referral channels. Reasons to prompt referral to mental health include complicated depression such as with psychosis, clinical suspicion for other psychiatric diseases such as bipolar disorder, suicidal ideation, or treatment-resistant depression (Figure 1). Paying attention to the presence of acute suicidal intent in depressed patients is particularly important in order to rule out immediate threat to themselves or others, and needs to be integrated into the patient evaluation. Once the diagnosis of clinical depression is made, treatment options need to be tailored to the individual needs of the patient and the resources available to the clinical team or dialysis facility (Figure 1). Thus, the care of each patient needs to be individually assessed and a treatment plan developed. There are a variety of treatment options available (discussed below), but few studies guide us as to the best evidence-based approach. In the following section, we review the pharmacologic and nonpharmacologic approaches to treating depression that have been suggested and studied in this patient population. Patients with moderate to advanced CKD and ESRD have generally been excluded from large antidepressant trials because of concerns for adverse events and the paucity of data on safety of antidepressants in this population.26.Glassman A.H. O′Connor C.M. Califf R.M. et al.Sertraline treatment of major depression in patients with acute MI or unstable angina.JAMA. 2002; 288: 701-709Crossref PubMed Scopus (1243) Google Scholar This likely has contributed to the undertreatment and underdosing of antidepressant medications in CKD patients. In fact, few studies have critically examined the pharmacologic treatment of depression in CKD patients. Antidepressant medications are generally highly protein bound and not removed significantly by the dialysis procedure.27.Micromedex® Healthcare Series [intranet database]. Version 5.1. Thomson Healthcare: Greenwood Village, CO.Google Scholar,28.Cohen S.D. Perkins V. Kimmel P.L. Psychosocial issues in ESRD patients.in: Daugirdas J. Ing T. Handbook of Dialysis. 4th edn. Little Brown, Boston2007: 455-461Google Scholar They commonly undergo hepatic metabolism, but many have active metabolites that are renally excreted, leading to accumulation of potentially toxic metabolites in patients with decreased glomerular filtration rates.27.Micromedex® Healthcare Series [intranet database]. Version 5.1. Thomson Healthcare: Greenwood Village, CO.Google Scholar,28.Cohen S.D. Perkins V. Kimmel P.L. Psychosocial issues in ESRD patients.in: Daugirdas J. Ing T. Handbook of Dialysis. 4th edn. Little Brown, Boston2007: 455-461Google Scholar In addition, there is the risk of drug–drug interactions in CKD and ESRD patients who, because of a large burden of comorbidities and metabolic derangements, are already on many medications. Several classes of antidepressants such as serotonin modulators, tricyclics, and tetracyclics have cardiac side effects such as QTc prolongation, arrhythmias, and orthostatic hypotension (Table 2). Given that a large proportion of patients with CKD and ESRD suffer from cardiovascular (CV) disease, use of such medications without clinical trials to advocate safety must be carefully considered. Central nervous system depression is also a common adverse event. Increased bleeding risk was reported in association with serotonin-selective reuptake inhibitors (SSRIs),29.Dalton S.O. Johansen C. Mellemkjaer L. Use of selective serotonin reuptake inhibitors and risk of gastrointestinal bleeding: a population-based cohort study.Arch Intern Med. 2003; 163: 59-64Crossref PubMed Scopus (334) Google Scholar which may become problematic in advanced CKD and underlying platelet dysfunction related to uremia. Finally, the serotonergic gastrointestinal activity of SSRIs, one of the most commonly used antidepressant classes, can result in nausea and vomiting, which again may exacerbate these symptoms in patients with predialysis stage 5 CKD and ESRD.27.Micromedex® Healthcare Series [intranet database]. Version 5.1. Thomson Healthcare: Greenwood Village, CO.Google Scholar,30.Cohen S.D. Norris L. Acquaviva K. et al.Screening, diagnosis, and treatment of depression in patients with end-stage renal disease.Clin J Am Soc Nephrol. 2007; 2: 1332-1342Crossref PubMed Scopus (160) Google ScholarTable 2Antidepressant medication classes and dosing in CKDMedication class and dosing in normal eGFRDosing in CKD and ESRDPotential class adverse effects32.Wuerth D. Finkelstein S.H. Finkelstein F.O. The identification and treatment of depression in patients maintained on dialysis.Semin Dial. 2005; 18: 142-146Crossref PubMed Scopus (106) Google ScholarSelective serotonin reuptake inhibitors Sertraline 50–200mg/day, single doseNo dose adjustment recommended, but active metabolite is renally excretedIncreased risk of bleeding; GI symptoms including nausea and diarrhea; CNS effects; sexual dysfunction; hyponatremia ParoxetineImmediate-release 20–50mg/day, single doseControlled-release 25–62.5mg/day, single doseElimination half-life prolonged if CrCl <30ml/minImmediate-release: 10mg/day initial dose, max 40mg/dayControlled-release: 12.5mg/day initial dose, max 50mg/day Fluoxetine 20–80mg/day, single doseNo dose adjustment recommended, but long half-life; use with caution Citalopram 20–40mg/day, single doseInitial dose 10mg/day; active metabolite. Not recommended for eGFR <20ml/minHigher citalopram doses associated with QTc prolongation, torsades de pointes Escitalopram 10–20mg/day, single doseUse with caution in severe renal impairmentDopamine/norepinephrine reuptake inhibitors Bupropion 200mg/day, 2 divided dosesMax 450mg/day, 3–4 divided dosesActive metabolite; reduce frequency and/or doseAccumulation of toxic metabolites; cardiac dysrhythmia; wide QRS complex; nausea, insomnia, dizzinessNoradrenergic and serotonergic agonist Mirtazapine 15–45mg/day at bedtimeReduce dose; clearance reduced by 30% if CrCl 11–39ml/min, and by 50% if CrCl <10CNS effects including somnolence; weight gainTricyclics and tetracyclics (TCAs) Amitriptyline 75–150mg/day, 1–3 divided dosesGenerally avoid TCAs given cardiac side effectsNo dosage adjustment recommendedQTc prolongation, arrhythmias, orthostatic hypotension; CNS and anticholinergic effects Desipramine 100–300mg/day, singly or dividedCaution advised if eGFR <15ml/min; avoid given cardiac side effects Doxepin 25–300mg/day, singly or dividedNo dosage adjustment recommended Nortriptyline 25mg/day, 3 to 4 times dailyMax 150mg/dayNo dosage adjustment recommendedSerotonin/norepinephrine reuptake inhibitors VenlafaxineImmediate-release 75–225mg/day, 2–3 divided Extended-release 37.5–225mg/day, singlyReduce dose by 25 to 50% in patients with mild-to-moderate renal impairmentHypertension, sexual dysfunction, neuroleptic malignant syndrome, serotonin syndrome, accumulation of toxic metabolite O-desmethylvenlafaxineSerotonin modulators Nefazodone 100–600mg/day, 2 divided dosesGenerally avoid in cardiovascular or liver diseaseIncrease dose carefullyCardiac dysrhythmias, Stevens–Johnson syndrome, liver failure, serotonin syndrome, priapism TrazodoneImmediate-release 150–400mg/day, dividedIncrease dose carefully; use divided doses in elderlyExtended-release 150–375mg/day, singly at nightMonoamine oxidase inhibitors (MAOIs) Phenelzine 45–90mg/day, 3 divided dosesAvoid MAOI in CKD because of drug–drug interactions, although no dose adjustment advised for mild-to-moderate renal impairmentSignificant drug–drug interactions; risk of hypertensive crisis with tyramine-rich foods; orthostatic hypotension Selegiline transdermal patch, 6mg per 24h, may increase every 2 weeks by 3mg per 24h up to 12mg per 24hAbbreviations: CKD, chronic kidney disease; CNS, central nervous system; CrCl, creatinine clearance; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; GI, gastrointestinal.Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies with major depressive disorder and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24 years, and there was a reduction in risk with antidepressants compared with placebo in adults aged ≥65 years.27.Micromedex® Healthcare Series [intranet database]. Version 5.1. Thomson Healthcare: Greenwood Village, CO.Google Scholar Open table in a new tab Abbreviations: CKD, chronic kidney disease; CNS, central nervous system; CrCl, creatinine clearance; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; GI, gastrointestinal. Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies with major depressive disorder and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24 years, and there was a reduction in risk with antidepressants compared with placebo in adults aged ≥65 years.27.Micromedex® Healthcare Series [intranet database]. Version 5.1. Thomson Healthcare: Greenwood Village, CO.Google Scholar There are insufficient data to clearly suggest that treatment of major depressive disorder is either efficacious or changes outcomes in advanced CKD and ESRD patients.3.Hedayati S.S. Bosworth H.B. Kuchibhatla M. et al.T
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